Predictive value of molecular subtyping in NMIBC by RT-qPCR of ERBB2, ESR1, PGR and MKI67 from formalin fixed TUR biopsies

Breyer, Johannes and Wirtz, Ralph Markus and Otto, Wolfgang and Laible, Mark and Schlombs, Kornelia and Erben, Philipp and Kriegmair, Maximilian Christian and Stoehr, Robert and Eidt, Sebastian and Denzinger, Stefan and Burger, Maximilian and Hartmann, Arndt (2017) Predictive value of molecular subtyping in NMIBC by RT-qPCR of ERBB2, ESR1, PGR and MKI67 from formalin fixed TUR biopsies. ONCOTARGET, 8 (40). pp. 67684-67695. ISSN 1949-2553,

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Abstract

Expression of ESR1, PGR, HER2 and Ki67 is important for risk stratification and therapy in breast cancer. Hormone receptor expression can also be found in MIBC, reflecting luminal and basal subtypes of breast cancer. Thus the purpose was to investigate on the mRNA expression of the aforementioned markers and their prognostic value in pT1 bladder cancer. Retrospective analysis of clinical data and Formalin-Fixed Paraffin-Embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder was performed. mRNA expression was measured by single step RT-qPCR. Relative gene expression was determined by normalization to two housekeeping genes (CALM2, B2M) using the 40-Delta Delta CT method. Correlation of mRNA expression with outcome was assessed using Kaplan-Meier analysis and multivariate Cox regression analysis. From overall 302 patients, 255 samples could be analyzed with valid measurements. Subtype distribution was Luminal-A in 11.4%, Luminal-B in 38.8%, triple negative in 36.9% and ERBB2 in 12.9%, respectively. Kaplan-Meier analysis revealed molecular subtyping being statistical significant for RFS (p=0.0408) and PFS (p=0.0039). Luminal-A patients did have the best RFS and PFS. Multivariate analysis revealed molecular subtyping to be significant for PFS (L-R Chi(2) of 11.89, p=0.0078). Elevated expression of HER2 was statistically significant for PFS (p=0.0025) and discriminated among G3 tumors a high risk group (60% PFS) from a low risk risk group (90% PFS) after 5 year follow-up (p<0.001). Expression of ESR1, PGR and HER2 has predictive value in stage pT1 NMIBC and reveals potential therapeutic targets.

Item Type: Article
Uncontrolled Keywords: INVASIVE BLADDER-CANCER; BACILLUS-CALMETTE-GUERIN; UROTHELIAL CARCINOMA; BREAST-CANCER; RISK STRATIFICATION; LUMINAL SUBTYPES; PROGNOSTIC VALUE; STAGE; PROGRESSION; MARKERS; molecular subtypes; non-muscle-invasive bladder cancer; prognosis; RT-qPCR; mRNA
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Urologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 14 Dec 2018 13:15
Last Modified: 28 Feb 2019 06:57
URI: https://pred.uni-regensburg.de/id/eprint/1179

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